TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15845	47758;47759;47760	chr2:178617818;178617817;178617816	chr2:179482545;179482544;179482543
N2AB	14204	42835;42836;42837	chr2:178617818;178617817;178617816	chr2:179482545;179482544;179482543
N2A	13277	40054;40055;40056	chr2:178617818;178617817;178617816	chr2:179482545;179482544;179482543
N2B	6780	20563;20564;20565	chr2:178617818;178617817;178617816	chr2:179482545;179482544;179482543
Novex-1	6905	20938;20939;20940	chr2:178617818;178617817;178617816	chr2:179482545;179482544;179482543
Novex-2	6972	21139;21140;21141	chr2:178617818;178617817;178617816	chr2:179482545;179482544;179482543
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-2
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1688
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
S/N	None	None	0.999	D	0.895	0.622	0.459370960843	gnomAD-4.0.0	1.36944E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79995E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
S/A	0.3758	ambiguous	0.2604	benign	-0.716	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
S/C	0.5831	likely_pathogenic	0.373	ambiguous	-0.749	Destabilizing	1.0	D	0.878	deleterious	D	0.728051491	None	None	N
S/D	0.9886	likely_pathogenic	0.9872	pathogenic	-1.096	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
S/E	0.9933	likely_pathogenic	0.9909	pathogenic	-1.042	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
S/F	0.9804	likely_pathogenic	0.9686	pathogenic	-0.598	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
S/G	0.4394	ambiguous	0.3105	benign	-1.016	Destabilizing	0.999	D	0.888	deleterious	D	0.649545736	None	None	N
S/H	0.984	likely_pathogenic	0.9767	pathogenic	-1.454	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
S/I	0.9538	likely_pathogenic	0.9127	pathogenic	-0.005	Destabilizing	1.0	D	0.907	deleterious	D	0.784542148	None	None	N
S/K	0.9985	likely_pathogenic	0.9973	pathogenic	-0.979	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
S/L	0.8531	likely_pathogenic	0.7505	pathogenic	-0.005	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
S/M	0.9302	likely_pathogenic	0.8864	pathogenic	0.085	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/N	0.9477	likely_pathogenic	0.9072	pathogenic	-1.128	Destabilizing	0.999	D	0.895	deleterious	D	0.784102032	None	None	N
S/P	0.9851	likely_pathogenic	0.9828	pathogenic	-0.207	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
S/Q	0.9892	likely_pathogenic	0.9828	pathogenic	-1.199	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
S/R	0.996	likely_pathogenic	0.9913	pathogenic	-0.926	Destabilizing	1.0	D	0.881	deleterious	D	0.724948464	None	None	N
S/T	0.3209	likely_benign	0.3358	benign	-0.983	Destabilizing	0.999	D	0.894	deleterious	D	0.668664857	None	None	N
S/V	0.887	likely_pathogenic	0.8209	pathogenic	-0.207	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
S/W	0.9885	likely_pathogenic	0.9841	pathogenic	-0.669	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
S/Y	0.9805	likely_pathogenic	0.9662	pathogenic	-0.377	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.